In this proposal, we are aiming to study nox5, a calcium-sensitive NAD(P)H oxidase, and determine its role in vascular smooth muscle growth and migration. Previous work in this laboratory has shown that NAD(P)H oxidases are active participants in angiotensin II signaling events. Nox5 is a member of the non-phagocytic NAD(P)H oxidases that has been shown to produce large amounts of superoxide in response to calcium. In this proposal, we have 2 specific aims: 1) to confirm that nox5 produces superoxide in a calcium-sensitive manner, and 2) to determine the role of nox5 in vascular smooth muscle growth and migration. We will use overexpression and antisense strategies in order to achieve these aims. Future experiments may involve an animal restenosis model or transgenic studies. The results may have implications for the treatment of clinically important conditions such as atherosclerosis and post angioplasty restenosis.